Understanding AL Amyloidosis

Introduction to AL Amyloidosis

AL amyloidosis was previously known as primary amyloidosis and is currently the most common type of amyloidosis in developed countries. In the UK about 500-600 new cases are diagnosed each year and it is the cause of death in between 0.5 to 1 out of every 1000 people. This is the diagnosis in about 60% of the patients treated at the NAC and this condition is never hereditary. AL amyloidosis is commoner in men than in women and although most patients with AL amyloidosis are aged over 45, it occasionally occurs at younger ages.

Patients with AL amyloidosis have an underlying disorder in which there is overproduction of amyloidogenic proteins called light chains.

heavy and light chains in antibodies

Each normal antibody consists of 4 protein chains. The red chains in this illustration are called the “light chains” and the grey chains are called the “heavy chains”.

Light chains are parts of antibodies, also known as immunoglobulins. They are produced by a type of immune system cell called plasma cells. In AL amyloidosis abnormal plasma cells produce amyloidogenic light chains or light chain fragments. The light chains or light chain fragments form amyloid deposits in the tissues. The abnormal plasma cells are usually, but not always, located in the bone marrow

The “L” in the name AL amyloidosis stands for “light chain.”

Abnormal free light chains can be measured in the blood in about 95% of patients with AL amyloidosis.

The bone marrow

The bone marrow is the inner part of the bones. In healthy people, the bone marrow produces blood cells and plays an important role in defence against disease, as it is the site where many of the cells of the immune system grow and mature. The immune system defends the body from diseases of all types.

Adapted from illustration by Ewa Sitnicka, Stem Cell Center, Lund University, Sweden, reproduced with permission

Adapted from illustration by Ewa Sitnicka, Stem Cell Center, Lund University, Sweden, reproduced with permission

Normal plasma cells, B cells and antibodies

Different immune system cells have different functions and one such cell type, called plasma cells, fight disease by producing antibodies against the vast array of infectious germs (that is bacteria and viruses, known as pathogens) that we encounter during our lives.

Antibodies act like specialised weapons, fitting tightly onto the pathogen, rather like two pieces of a jigsaw puzzle, or a key fitting into a lock. They thus immobilise the pathogen and other immune cells can then clear it from the body.

Plasma cells are formed from another type of white blood cell called B cells. Each B cell in the body is unique and has the capacity to produce its own unique antibodies, but this potential is only unlocked when it encounters a pathogen that is a close fit. Then the B cell begins to divide and form many identical cells. These identical cells are called a “clone” of plasma cells, and they sit in the bone marrow and act like little antibody production factories, churning out huge quantities of identical antibodies into the bloodstream, to seek out and destroy the pathogen they fit so well.

Normal plasma cells, B cells and antibodies

In a healthy person, antibodies are broken down inside the body once they have done their job of fighting infection and antibody production by plasma cells shuts down almost completely once the pathogen has been overcome.

Abnormal cell function and AL amyloidosis

In AL amyloidosis a line, or clone, of identical B cells or plasma cells behaves abnormally, continuously producing large quantities of just one part, or fragment, of a particular antibody called a monoclonal immunoglobulin light chain.

Normal B cells and plasma cells stop multiplying and producing antibodies once the body has recovered from an infection, but in the B cell/plasma cell disorders the cells do not shut down as and when they should, but instead continue to churn out antibodies or antibody fragments (light chains) into the bloodstream. These abnormal proteins do not serve any defence function against disease, but in many cases they also do no harm.

AL amyloidosis develops when the abnormal proteins produced (usually light chains or fragments of light chains) are amyloidogenic. This means that they aggregate (clump) together in the tissues in the form of long thread-like fibres that the body cannot easily destroy and clear away. These fibrous aggregates are the amyloid fibrils which form amyloid deposits and as they accumulate in the tissues of the body they disrupt the structure and function of whichever organs are involved.

Most patients with AL amyloidosis have relatively low numbers of abnormal plasma cells in the bone marrow but this can be variable. 15% of patients with AL amyloidosis can have many abnormal plasma cells in the bone marrow which may be directly damaging to bones or affect the function of the bone marrow.